Morbidity and Mortality Related to Gastric Bypass Surgery This renewal application proposes a continuation of the longest prospective gastric bypass surgery study in the world. Potential beneficiaries of this research include the estimated 24 million Americans with severe obesity (BMIe35 kg/m2), an obesity status that often has early onset, is a strong risk factor for disease and early mortality, is difficult to treat, and is highly resistant to traditional methods for achieving meaningful weight loss and weight loss maintenance. To date, the only effective long-term treatment of severe obesity is bariatric surgery. Gastric bypass represents the most common weight loss surgical procedure in the U.S., and laparoscopic adjustable gastric banding surgery is the second most popular alternative. Gastric bypass surgery results in greater weight loss than the gastric banding procedure, allowing a better evaluation of weight-loss effects on cardiovascular risk factors and subclinical atherosclerosis. In addition, gastric bypass surgery leads to an almost immediate remission of diabetes - even before weight loss - suggesting potential avenues of research to prevent or perhaps cure diabetes. The 10-year follow-up of this cohort of severely obese subjects who have (N=418) or have not (N=738) had gastric bypass surgery will allow surgeons and patients to assess the long-term risks of this surgery and to identify which of the cardiovascular and other obesity-related risk factors would be expected to improve, how long the health improvements might last, and whether or not maintaining improvement is dependent on maintaining post-surgical weight loss. This study will also indicate how the heart is benefitted by gastric bypass surgery and whether or not development of subclinical atherosclerosis is retarded by maintained weight loss. Clinical measurements will include biochemical measures, blood pressure, resting metabolic rate, fitness- and diet-related parameters, overnight sleep studies, and anthropometrics. Echocardiograms for left ventricular hypertrophy, heart structure and function, CT scans for coronary calcium, epicardial fat and visceral fat, as well as arterial stiffness will be obtained to relate to the risk factors measured. Changes in body weight from baseline to the year 2 exam and weight regain since year 2 (i.e., to year 10) will be related to risk factor changes. Finally, further follow-up of our new observation that gastric bypass patients are more prone to post-surgical problems such as suicide, drug overdose, or accidents is required to be able to assess how and to what extent counseling should be provided to these subjects to prevent this newly-identified post-surgical risk. Therefore, this grant is highly based on translational science to improve the management and counseling of potential and post-surgical severely obese patients. PUBLIC HEALTH RELEVANCE: The 10-year follow-up of this cohort of severely obese subjects who have or have not had gastric bypass surgery will allow surgeons and patients to assess the long-term risks of this surgery and which of the cardiovascular risk factors they may suffer from would be expected to improve. It will also indicate how the heart is benefitted by this surgery and how permanent these changes are, as long as the surgical weight loss is maintained. The importance of maintaining post-surgical weight loss will be an important outcome of this research.